Incorporation of phencyclidine and its hydroxylated metabolites into hair.
The incorporation of phencyclidine(PCP) and its three major hydroxylated metabolites, 1-(1-phenylcyclohexyl)-4-hydroxypiperidine(PCHP), trans-4-phenyl-4-piperidinocyclohexanol(t-PPC) and trans-1-phenyl-1-(4'-hydroxypiperidino)-4-cyclohexanol(t-PCPdiol) into rat hair was studied. Three Dark Agouti male rats were intraperitoneally administered with PCP x HCl at a dose of 0.5 or 1.0 mg/kg once a day for 10 successive days. The plasma samples were collected from 5 min to 360 min after injection of each drug. The hair samples were collected 28 days after the first administration. The hair samples were extracted with methanol-5N hydrochloric acid(20:1) for 1 h under sonication. The plasma and hair extracts were extracted or purified with Bond Elut Certify and the extracts were silylated for the determination of PCP and its metabolites by GC/MS. The plasma AUCs were as follows; PCP(2.03 microg x min/ml) > t-PCPdiol(0.60 microg x min/ml) > PCHP(0.11 microg x min/ml) > t-PPC (0.065 microg x min/ml), while the hair concentrations were as follows; PCP(7.51 ng/mg) > PCHP (1.22 ng/mg) > t-PPC(0.10 ng/mg) > t-PCPdiol (0.05 ng/mg). In view of their AUCs, the hair concentration of t-PCPdiol was quite low, whereas that of PCP was so high. PCHP, t-PPC or t-PCPdiol was separately administered as the parent drug to the rats, and then the plasma and hair samples were analyzed in the same manner as PCP experiments. The incorporation rates ([hair concentration]/[AUC]) of PCP and its hydroxylated metabolites were as follows; PCP(2.29) > PCHP(0.79) > t-PPC(0.36) > t-PCPdiol(0.32). These data suggest that the decrease in lipophilicity caused by the hydroxylation of PCP suppresses the incorporation of the metabolites from blood into hair and the hydroxylation on cyclohexane ring(t-PPC) induces the decrease of the drug incorporation into hair more than that on piperidine ring(PCHP).
Sakamoto
T
T
Showa College of Pharmaceutical Sciences, Machida, Tokyo, Japan.
Tanaka
A
A
Nakahara
Y
Y
D000818:Animals; D006197:Hair / Q000378:metabolism*; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats
C031108:1-(1-phenylcyclohexyl)-4-hydroxypiperidine; D010622:Phencyclidine